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PURPOSE: The incidence of breast cancer in young women (BCYW) has increased in recent decades. Malignant disease in this subset is characterized by its aggressiveness and poor prognosis. Ovarian function suppression (OFS) in these patients improves survival especially in hormone receptor-positive (HR +) cases. The Regan Composite Risk (RCR) is a prognostic tool to identify high-risk HR + BC candidates for OFS. Our study sought to characterize a Chilean cohort of early HR + BCYW assessing the use of OFS and its related prognosis and the utility of RCR in our patients. METHODS: This was a retrospective population cohort study that included ≤ 35-year-old early HR + /human epidermal growth factor receptor 2 -negative (HER2-) BC patients treated between 2001 and 2021. Analysis included clinical-pathological characteristics, treatment strategies, and survival. Also, we evaluated the association between RCR and survival. RESULTS: A total of 143 patients were included into our study, representing 2.9% of all early BC cases in our registry. Median age was 31 years old (range: 19-35). Most patients (93%) received endocrine therapy (ET). Of these, 18% received OFS. No survival differences were observed among treatment strategies. Median RCR score for patients treated with CT plus ET was significantly higher vs. ET alone (2.95 vs. 1.91; p = 0.0001). Conversely, patients treated with tamoxifen alone had significantly lower RCR scores vs. OFS (2.72 vs. 3.14; p = 0.04). Higher RCR scores were associated with poorer overall survival. CONCLUSION: Less than 20% of very young women with early HR + /HER2-BC in our cohort received OFS, in most cases, this involved surgical oophorectomy. RCR score was higher in patients that underwent CT and OFS and was associated with survival, regardless of treatment. We confirm the RCR score as a valuable prognostic tool to identify high-risk BC patients who could benefit from OFS.
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Neoplasias de la Mama , Femenino , Humanos , Adulto , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Antineoplásicos Hormonales/uso terapéutico , Estudios Retrospectivos , Estudios de Cohortes , Quimioterapia Adyuvante , Premenopausia , Receptor ErbB-2/metabolismoRESUMEN
BACKGROUND: Latin American (LA) studies on triple-negative breast cancer (TNBC) and their characteristics are scarce. This forces physicians to make clinical decisions based on data obtained from studies that include non-Hispanic patients. Our study sought to obtain local epidemiological data, including risk factors and clinical outcomes from a Chilean BC registry. METHODS: This was a retrospective population-cohort study that included patients treated at a community hospital (mid-low income) or an academic private center (high income), in the 2010-2021 period. Univariate and multivariate analyses were performed to identify prognostic factors associated with survival. RESULTS: 647 out of 5,806 BC patients (11.1%) were TNBC. These patients were younger (p = 0.0001) and displayed lower rates of screening-detected cases (p = 0.0001) compared to non-TNBC counterparts. Among TNBC patients, lower income (i. e., receiving treatment at a community hospital) was associated with poorer overall survival (HR: 1.53; p = 0.0001) and poorer BC specific survival (HR: 1.29; p = 0.004). Other risk factors showed no significant differences between TNBC and non-TNBC. As expected, 5-year OS was significantly shorter on TNBC versus non-TNBC patients (p = 0.00001). In our multivariate analyses TNBC subtype (HR: 2.30), locally advanced stage (HR: 7.04 for stage III), lower income (HR: 1.64), or non-screening detected BC (HR: 1.32) were associated with poorer OS. CONCLUSION: To the best of our knowledge, this is the largest LA cohort of TNBC patients. Interestingly, the proportion of TNBC among Chileans was smaller compared to similar studies within LA. As expected, TNBC patients had poorer survival and higher risk for early recurrence versus non-TNBC. Other relevant findings include a higher proportion of premenopausal patients among TNBC. Also, mid/low-income patients that received medical attention at a community hospital displayed lower survival versus private health center counterparts.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/epidemiología , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/diagnóstico , Chile/epidemiología , Factores de Riesgo , PronósticoRESUMEN
PURPOSE: Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristics to explore improvement strategies. METHODS: Retrospective analysis of invasive BC databases including patients treated in a Public Hospital (PH) and in an Academic Private Center (AC) in Santiago, Chile between 2012 and 2021. RESULTS: Of 5438 BC patients, 3955 had enough data for National Comprehensive Cancer Network (NCCN) categorization. From these, 1911 (48.3%) fulfilled NCCN criteria for germline testing, of whom, 300 were tested for germline mutations and 268 with multigene panels. A total of 65 pathogenic variants were found in this subset. As expected, BRCA1/2 mutations were the most frequent (17.7%). Access to genetic testing was higher in AC versus PH (19.6% vs. 10.3%, p = 0.0001). Other variables associated with germline genetic testing were BC diagnosis after 2018, being 45 years old or younger at diagnosis, BC family history (FH), FH of ovarian cancer, non-metastatic disease, and triple-negative subtype. CONCLUSION: In our cohort, 15% of BC patients who met NCCN criteria for germline testing were effectively tested. This percentage was even lower at the PH. Current recommendations encourage universal genetic testing for BC patients; however, our findings suggest that Chile is far from reaching such a goal and national guidelines in this regard are urgently needed. To our knowledge, this is the first study of its kind in Chile and Latin America.
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Neoplasias de la Mama , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Proteína BRCA1/genética , Chile/epidemiología , Estudios Retrospectivos , Predisposición Genética a la Enfermedad , Proteína BRCA2/genética , Pruebas Genéticas , Mutación de Línea GerminalRESUMEN
Sodium metal is a promising anode material for room-temperature sodium sulfur batteries. Due to its high reactivity, typical liquid electrolytes (e.g. carbonate-based solvents and a Na salt) can undergo reduction to form a solid electrolyte interphase (SEI) layer, with inorganic components such as Na2CO3, Na2O, and NaOH, covering the anode surface along with other SEI organic products. One of the challenges is to understand the effect of the SEI film on the decomposition of soluble sodium polysulfide molecules (e.g., Na2S8) upon shuttling from the cathode to anode during battery cycling. Here, we use ab initio molecular dynamics (AIMD) simulations to study the role of an inorganic SEI used as a model passivation layer in polysulfide decomposition. Compared to other film chemistries, it is found that the Na2CO3 film can suppress decomposition with the slowest reduction rate and the smallest amount of charge transfer towards Na2S8. The Na2CO3 film can maintain its structural properties during the simulations. In contrast, Na2O and NaOH allow some decomposed polysulfide fragments to be inserted into the SEI layer. Moreover, the decomposition of Na2S8 on both Na2O and NaOH SEI layers is more reactive with more charge transfer to Na2S8 when compared to that of Na2CO3. Thus, the ability of the SEI to suppress polysulfide decomposition is in the order: Na2CO3 > NaOH â¼ Na2O. Analyses of the density of states reveal that the Na2S8 molecule receives electrons from the Na metal directly in the presence of n-type semiconductor films of Na2CO3 and NaOH, while the charge migration behavior is different in a p-type semiconductor Na2O with the SEI film donating its electrons to the polysulfide solely. Thus, this work adds new insights into charge transfer behavior of inorganic thin film SEIs that could be present at the initial stages of SEI formation.
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Epidermolysis bullosa (EB) is an inherited disorder characterised by skin fragility and the appearance of blisters and wounds. Patient wounds are often colonised or infected with bacteria, leading to impaired healing, pain and high risk of death by sepsis. Little is known about the impact of bacterial composition and susceptibility in wound resolution, and there is a need for longitudinal studies to understand healing outcomes with different types of bacterial colonisation. A prospective longitudinal study of 70 wounds from 15 severe EB patients (Junctional and Recessive Dystrophic EB) from Chile. Wounds were selected independently of their infected status. Wound cultures, including bacterial species identification, composition and Staphylococcus aureus (SA) antibiotic susceptibility were registered. Wounds were separated into categories according to their healing capacity, recognising chronic, and healing wounds. Hundred-one of the 102 wound cultures were positive for bacterial growth. From these, 100 were SA-positive; 31 were resistant to Ciprofloxacin (31%) and only seven were methicillin-resistant SA (7%). Ciprofloxacin-resistant SA was found significantly predominant in chronic wounds (**P < .01). Interestingly, atoxigenic Corynebacterium diphtheriae (CD) was identified and found to be the second most abundant recovered bacteria (31/101), present almost always in combination with SA (30/31). CD was only found in Recessive Dystrophic EB patients and not related to wound chronicity. Other less frequent bacterial species found included Pseudomonas aeruginosa, Streptococus spp. and Proteus spp. Infection was negatively associated with the healing status of wounds.
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Corynebacterium diphtheriae , Epidermólisis Ampollosa Distrófica , Epidermólisis Ampollosa , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus , Estudios Longitudinales , Estudios Prospectivos , Epidermólisis Ampollosa/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico , Cicatrización de Heridas , Ciprofloxacina , Epidermólisis Ampollosa Distrófica/complicacionesRESUMEN
PURPOSE: The implementation of national breast cancer (BC) screening programs in Latin America has been rather inconsistent. Instead, most countries have opted for "opportunistic" mammogram screenings on the population at risk. Our study assessed and compared epidemiological, clinical factors, and survival rates associated with BC detected by screening (SDBC) or self-detected/symptomatic (non-SDBC) in Chilean female patients. METHODS: Registry-based cohort study that included non-metastatic BC (stage I/II/III) patients diagnosed between 1993 and 2020, from a public hospital (PH) and a private university cancer center (PC). Epidemiological and clinical data were obtained from medical records. RESULTS: A total of 4559 patients were included. Most patients (55%; n = 2507) came from PH and were diagnosed by signs/symptoms (non-SDBC; n = 3132, 68.6%); these patients displayed poorer overall (OS) and invasive disease-free survival (iDFS) compared to SDBC. Importantly, the proportion of stage I and "luminal" BC (HR + /HER2 -) were significantly higher in SDBC vs. non-SDBC. Finally, using a stage/subset-stratified age/insurance-adjusted model, we found that non-SDBC cases are at a higher risk of death (HR:1.75; p < 0.001). In contrast, patients with PC health insurance have a lower risk of death (HR: 0.60; p < 0.001). CONCLUSION: We confirm previous studies that report better prognosis/survival on SDBC patients. This is probably due to a higher proportion of stage I and luminal-A cases versus non-SDBC. In turn, the survival benefit observed in patients with PC health insurance might be attributed to a larger proportion of SDBC. Our data support the implementation of a systematic BC screening program in Chile to improve patient prognosis and survival rates.
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Neoplasias de la Mama , Detección Precoz del Cáncer , Tamizaje Masivo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Chile/epidemiología , Estudios de Cohortes , Femenino , Humanos , Mamografía , Pronóstico , Receptor ErbB-2RESUMEN
BACKGROUND: Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage. METHODOLOGY: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage. DISCUSSION: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.
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Cardiotoxicidad/diagnóstico por imagen , Ecocardiografía/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias/radioterapia , Traumatismos por Radiación/diagnóstico , Neoplasias de la Mama/radioterapia , Cardiotoxicidad/etiología , Protocolos Clínicos , Células Endoteliales , Neoplasias Esofágicas/radioterapia , Femenino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Contracción Miocárdica/fisiología , Péptido Natriurético Encefálico/análisis , Fragmentos de Péptidos/análisis , Dosis de Radiación , Volumen Sistólico , Troponina T/análisis , Disfunción Ventricular IzquierdaRESUMEN
BACKGROUND: About 80% of breast cancer (BC) cases express estrogen receptor (ER), which has been correlated with good prognosis and response to estrogen deprivation Aim: To characterize ER positive advanced BC (ABC) patients treated at our institution assessing the impact of clinical pre-sentation (stage IV, de novo disease at diagnosis versus systemic recurrence) and BC subtype on survival rates. MATERIAL AND METHODS: We evaluated 211 ER+ advanced BC (ABC) patients, treated between 1997 and 2017. RESULTS: The median overall survival (OS) was 37 months. Median OS for the period 1997/2006 and 2007/2017 were 33 and 42 months, respectively (p = 0.47). Luminal A, ABC stage IV disease at diagnosis displayed better OS rates than Luminal B stage IV tumors (100 and 32 months respectively, p < 0.01). CONCLUSIONS: Clinical presentation (stage IV vs. systemic recurrence) and tumor subtype are key determinants of OS in ABC.
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Neoplasias de la Mama , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Estrógenos , Humanos , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de Progesterona , Tasa de SupervivenciaRESUMEN
PURPOSE: Atypical ductal hyperplasia (ADH) significantly increases the risk of breast cancer in women. However, little is known about the implications of ADH in men. METHODS: Review of 932 males with breast pathology was performed to identify cases of ADH. Patients were excluded if ADH was upgraded to cancer on excision, or if they had contralateral breast cancer. Cases were reviewed to determine whether any male with ADH developed breast cancer. RESULTS: Nineteen males were diagnosed with ADH from June 2003 to September 2018. All had gynecomastia. Surgical procedure was mastectomy in 8 patients and excision/reduction in 11. One patient had their nipple areola complex removed, and 1 required a free nipple graft. Median patient age at ADH diagnosis was 25 years (range 18-72 years). Of the 14 patients with bilateral gynecomastia, 10 had bilateral ADH and 4 had unilateral. Five cases of ADH were described as severe, bordering on ductal carcinoma in situ. No patient reported a family history of breast cancer. No patient took tamoxifen. At a mean follow-up of 75 months (range 4-185 months), no patient developed breast cancer. CONCLUSION: Our study is the first to provide follow-up information for males with ADH. With 6 years of mean follow-up, no male in our series has developed breast cancer. This suggests that either ADH in men does not pose the same risk as ADH in women or that surgical excision of symptomatic gynecomastia in men effectively reduces the risk of breast cancer.
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Ginecomastia/epidemiología , Ginecomastia/patología , Glándulas Mamarias Humanas/patología , Adolescente , Adulto , Anciano , Neoplasias de la Mama Masculina/epidemiología , Neoplasias de la Mama Masculina/etiología , Neoplasias de la Mama Masculina/patología , Carcinoma Ductal de Mama/epidemiología , Carcinoma Ductal de Mama/etiología , Estudios de Seguimiento , Ginecomastia/cirugía , Humanos , Hiperplasia , Masculino , Mastectomía , Persona de Mediana Edad , Vigilancia en Salud Pública , Riesgo , Adulto JovenRESUMEN
PURPOSE: Mammoplasty removes random samples of breast tissue from asymptomatic women providing a unique method for evaluating background prevalence of breast pathology in normal population. Our goal was to identify the rate of atypical breast lesions and cancers in women of various ages in the largest mammoplasty cohort reported to date. METHODS: We analyzed pathologic reports from patients undergoing bilateral mammoplasty, using natural language processing algorithm, verified by human review. Patients with a prior history of breast cancer or atypia were excluded. RESULTS: A total of 4775 patients were deemed eligible. Median age was 40 (range 13-86) and was higher in patients with any incidental finding compared to patients with normal reports (52 vs. 39 years, p = 0.0001). Pathological findings were detected in 7.06% (337) of procedures. Benign high-risk lesions were found in 299 patients (6.26%). Invasive carcinoma and ductal carcinoma in situ were detected in 15 (0.31%) and 23 (0.48%) patients, respectively. The rate of atypias and cancers increased with age. CONCLUSION: The overall rate of abnormal findings in asymptomatic patients undergoing mammoplasty was 7.06%, increasing with age. As these results are based on random sample of breast tissue, they likely underestimate the prevalence of abnormal findings in asymptomatic women.
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Neoplasias de la Mama/epidemiología , Mamoplastia , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Mama/patología , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Humanos , Hallazgos Incidentales , Massachusetts/epidemiología , Persona de Mediana Edad , Lesiones Precancerosas/patología , PrevalenciaRESUMEN
INTRODUCTION: Bilateral reduction mammoplasty is one of the most common plastic surgery procedures performed in the U.S. This study examines the incidence, management, and prognosis of incidental breast cancer identified in reduction specimens from a large cohort of reduction mammoplasty patients. METHODS: Breast pathology reports were retrospectively reviewed for evidence of incidental cancers in bilateral reduction mammoplasty specimens from five institutions between 1990 and 2017. RESULTS: A total of 4804 women met the inclusion criteria of this study; incidental cancer was identified in 45 breasts of 39 (0.8%) patients. Six patients (15%) had bilateral cancer. Overall, the maximum diagnosis by breast was 16 invasive cancers and 29 ductal carcinomas in situs. Thirty-three patients had unilateral cancer, 15 (45.5%) of which had high-risk lesions in the contralateral breast. Twenty-one patients underwent mastectomy (12 bilateral and nine unilateral), residual cancer was found in 10 in 25 (40%) therapeutic mastectomies. Seven patients did not undergo mastectomy received breast radiation. The median follow-up was 92 months. No local recurrences were observed in the patients undergoing mastectomy or radiation. Three of 11 (27%) patients who did not undergo mastectomy or radiation developed a local recurrence. The overall survival rate was 87.2% and disease-free survival was 82.1%. CONCLUSIONS: Patients undergoing reduction mammoplasty for macromastia have a small but definite risk of incidental breast cancer. The high rate of bilateral cancer, contralateral high-risk lesions, and residual disease at mastectomy mandates thorough pathologic evaluation and careful follow-up of these patients. Mastectomy or breast radiation is recommended for local control given the high likelihood of local recurrence without either.
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Neoplasias de la Mama/epidemiología , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/etiología , Neoplasias de la Mama/cirugía , Manejo de la Enfermedad , Femenino , Humanos , Incidencia , Mamoplastia/métodos , Persona de Mediana Edad , Clasificación del Tumor , Vigilancia en Salud Pública , Estudios Retrospectivos , Resultado del Tratamiento , Carga TumoralRESUMEN
We aim at elucidating the mechanism of the trimethyl aluminum (TMA) decomposition on oxidized nickel (NiO) and metallic nickel (Ni) facets in the absence of a source of hydroxyl groups. This TMA decomposition mechanism constitutes the earliest stage of growth of Al2O3 coatings with the atomic layer decomposition (ALD) method, which stabilizes nickel catalysts in energy-intensive processes such as the dry reforming of methane. Our first-principles calculations suggest thermodynamic favorability for the TMA decomposition on metallic nickel compared to oxidized nickel. Moreover, the decomposition of TMA on metallic nickel showed almost no differences in terms of energy barriers between flat and stepped surfaces. Regarding the impact of the CH3 radicals formed after TMA decomposition, we calculated stronger adsorption on metallic nickel facets than on oxidized nickel, and these adsorption energies are comparable to the adsorption energies calculated in earlier works on Al2O3 ALD growth on palladium surfaces. These results lead us to believe in the growth of porous Al2O3 coatings triggered by CH3 contamination rather than due to preferential TMA decomposition on stepped and/or defective facets. The CH3 radicals are likely to be thermally stable at temperatures used during Al2O3 ALD processes, partially passivating the surface towards further TMA decomposition.
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BACKGROUND: HER2+ breast cancer (BC) subtype overexpresses the Human Epidermal growth factor Receptor type-2 (HER2) and is characterized by its aggressiveness and its high sensitivity to monoclonal antibody-based HER2-targeted therapies. AIM: To assess the prognosis and evaluate the impact of novel anti-HER2 therapies on advanced HER2+ BC patients treated at our institution over the last decades. MATERIAL AND METHODS: Analysis of the patient database at a cancer center of a university hospital. Information about the subtype of cancer was obtained in 2,149 of 2,724 patients in the database. Eighteen percent of the latter were HER2+. We analyzed data of 83 of these patients with advanced disease. RESULTS: Median overall survival (OS) was 24 months. For patients treated between 1997-2006 median OS was 17 months and for those treated in the period 2007-2017 median OS was 32 months (p = 0.09). CONCLUSIONS: A non-significant trend towards better survival in the last decade was observed. HER2+ BC overall survival has improved in our center. This can be probably attributed to the use of novel more effective anti-HER2 therapies.
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Neoplasias de la Mama/química , Neoplasias de la Mama/mortalidad , Receptor ErbB-2/análisis , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Chile/epidemiología , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Lapatinib/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Receptor ErbB-2/antagonistas & inhibidores , Estudios Retrospectivos , Factores de Tiempo , Trastuzumab/uso terapéutico , Adulto JovenRESUMEN
In Chile breast cancer (BC) is the first cause of death in women. While the most important risk factor for its development is estrogenic stimulation, environmental factors and lifestyles also contribute to its pathogenesis. Epidemiological studies show a direct relationship between physical activity (PA), incidence and recurrence of BC. Supervised PA practice is recommended in most cancer patients to improve their quality of life, to reduce adverse effects from treatment and eventually to improve the prognosis of the disease. We review the epidemiological evidence linking PA and BC and the biological basis of this relationship. We also review the relevant interventional studies and we explore some practical indications of PA in patients with BC, as a model for other tumors of epidemiological importance.
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Neoplasias de la Mama/terapia , Ejercicio Físico , Neoplasias de la Mama/etiología , Neoplasias de la Mama/prevención & control , Femenino , Humanos , Estilo de Vida , Terapia Neoadyuvante , Calidad de Vida , Factores de RiesgoRESUMEN
Cutaneous melanoma is a highly aggressive tumor developing from melanocytes, its incidence is increasing, and prognosis in advanced stages is daunting. New therapies have been approved during the recent years with unprecedented results, including inhibitors of MAPK/ERK pathway and immune checkpoint blockade (anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) as ipilimumab, anti-programmed cell death protein 1 (PD-L1) as pembrolizumab and anti-programmed cell death protein 1 ligand (PD-L1), among many others). The aim of this paper is to review currently available metastatic melanoma therapies focusing mainly on new therapies that have demonstrated effectiveness, after several decades of little progress in the treatment of this disease.
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Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/secundario , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Melanoma/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Terapia Molecular Dirigida , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Neoplasias Cutáneas/genéticaRESUMEN
UNLABELLED: The white blood cell count is one of the most sensitive markers associated with inflammation. The neutrophil/lymphocyte count ratio may be an independent factor for breast cancer mortality. AIM: To assess the predictive value of the neutrophil/lymphocyte ratio for mortality in breast cancer. MATERIAL AND METHODS: Review of the database of a cancer center of a University hospital. Patients with infiltrating breast cancer treated between 1997 and 2012 were selected. The pathology type and lymph node involvement were obtained from the pathology report. The expression of estrogen, progesterone and Human Epidermal Growth Factor Receptor 2 (HER2) was determined by immunohistochemistry or in situ fluorescent hybridization (FISH). The absolute peripheral neutrophil and lymphocyte counts were obtained from a complete blood count obtained at least three months before treatment. Patients were followed for a median of 61 months (range 1-171). RESULTS: From 323 eligible patients, after excluding those in stage IV and those without an available complete blood count, 131 patients were analyzed (81 with negative receptors and 117 HER2 enriched). The neutrophil/lymphocyte ratio was similar in both types of tumors (2.1 and 1.91 respectively). Twenty two patients died during follow-up. Surviving patients with HER2 enriched tumors had a lower neutrophil/lymphocyte ratio than those who died (1.79 and 3.21 respectively, p < 0.01). In a multivariate analysis, including age, tumor stage and lymph node involvement as confounding factors, the neutrophil/lymphocyte ratio was still significantly associated with a risk of death with a hazard ratio of 2.56. CONCLUSIONS: A high neutrophil/lymphocyte ratio in the complete blood count can be a predictor of death in breast cancer.
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Neoplasias de la Mama/mortalidad , Linfocitos , Neutrófilos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Recuento de Células , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Recuento de Linfocitos , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
BACKGROUND: Pathological complete response (pCR) after neoadjuvant chemotherapy (NCT) in breast cancer (BC) identifies patients with good prognosis. AIM: To assess if the clinico-pathological subtype, determined by classic immunohistochemical (IHC) markers, is able to predict pCR and prognosis in BC patients treated with NCT. MATERIAL AND METHODS: One hundred thirty three BC patients aged 24-80 years, were treated with NCT. Clinico-pathological subtype was defined based on classic IHC markers. pCR was defined as the absence of invasive neoplastic cells in the breast and lymph nodes, on final breast surgery. RESULTS: pCR was achieved in 8.2% of patients, 3.5 and 19.5% in luminal and hormonal receptor (HR) negative tumors respectively (p < 0.01). Median follow-up was 72.6 months (3.5-190). Patients who achieved pCR had higher overall survival (OS) (p = 0.04). A univariate analysis revealed that size of the tumor, ratio of metastatic to examined lymph nodes and absence of HR were significant predictors of pCR. These findings were not replicated in the multivariate analyses. CONCLUSIONS: Clinico-pathological subtypes were independent prognostic factors for pCR and OS in BC patients in our cohort. These findings support using classic and cheap biomarkers as a predictive tool for NCT in BC.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Terapia Neoadyuvante , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Carga Tumoral , Adulto JovenRESUMEN
This study assesses the feasibility of calorie restriction (CR) and time-restricted feeding (TRF) in overweight and obese cancer patients who realized little to no physical activity undergoing curative radiotherapy, structured as a prospective, interventional, non-randomized open-label clinical trial. Of the 27 participants initially enrolled, 21 patients with breast cancer were selected for analysis. The participants self-selected into two dietary interventions: TRF, comprising a sugar and saturated fat-free diet calibrated to individual energy needs consumed within an 8 h eating window followed by a 16 h fast, or CR, involving a 25% reduction in total caloric intake from energy expenditure distributed across 4 meals and 1 snack with 55% carbohydrates, 15% protein, and 30% fats, excluding sugars and saturated fats. The primary goal was to evaluate the feasibility of these diets in the specific patient group. The results indicate that both interventions are effective and statistically significant for weight loss and reducing one's waist circumference, with TRF showing a potentially stronger impact and better adherence. Changes in the LDL, HDL, total cholesterol, triglycerides, glucose and insulin were not statistically significant.
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Neoplasias , Sobrepeso , Humanos , Sobrepeso/terapia , Restricción Calórica , Estudios Prospectivos , Obesidad/terapia , Neoplasias/complicaciones , Neoplasias/radioterapiaRESUMEN
The incidence of breast cancer in ≤ 40 yr-old women (YWBC) has been steadily increasing in recent decades. Although this group of patients represents less than 10 % of all newly diagnosed BC cases it encompasses a significant burden of disease. Usually underrepresented in clinical trials, YWBCs are also characterized by late diagnoses and poorly differentiated, aggressive-subtype disease, partly explaining its poor prognosis along with a high recurrence risk, and high mortality rates. On the other hand, YWBC treatment poses unique challenges such as preservation of fertility, and long-term toxicity and adverse events. Herein, we summarize the current evidence in hormone receptor-positive YWBC including specific risk factors, clinicopathologic and genomic features, and available evidence on response to chemotherapy and endocrine therapy. Overall, we advocate for a more comprehensive multidisciplinary healthcare model to improve the outcomes and the quality of life of this subset of younger patients.